Intramuscular and abdominal fat measured by computed tomography and mortality of hemodialysis patients.

BACKGROUND: In hemodialysis patients, high body mass index is associated with low mortality while abdominal obesity relates to increased mortality. We aimed to investigate the association between muscle mass, intramuscular fat and abdominal fat measured by abdominal computed tomography (CT), and mortality in this patients population. METHODS: This two-center retrospective cohort study included hemodialysis patients who underwent abdominal CT between January 2013 and December 2018. Skeletal muscle mass index (SMI), muscle radiation attenuation (MRA) as an index of intramuscular fat, and visceral fat to subcutaneous fat ratio (VSR) were calculated using CT images at the third lumbar vertebral level. Multivariate Cox proportional hazards model was used to determine the independent predictors of all-cause, cardiovascular and non-cardiovascular mortalities. RESULTS: The study included 344 patients (median age 71.0 years; female 33.7%), among whom 145 died during a median follow-up of 4.9 years-46 and 99 from cardiovascular and non-cardiovascular causes, respectively. Lower MRA [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.87, P = .001] and higher VSR (HR 1.17, 95% CI 1.01-1.37, P = .04) were independently associated with higher all-cause mortality but not with lower SMI (HR 0.87, 95% CI 0.68-1.11, P = .26). Lower MRA (HR 0.51, 95% CI 0.35-0.73, P < .001) and higher VSR (HR 1.29, 95% CI 1.09-1.54, P = .003) were also associated with cardiovascular and non-cardiovascular mortality, respectively. CONCLUSIONS: Intramuscular fat and abdominal fat as measured using abdominal CT in hemodialysis patients are stronger independent predictors of mortality than muscle mass.

Association of Postexercise Vagal Dysfunction With Protein-Energy Wasting and Noncardiovascular Outcomes in Patients Receiving Hemodialysis: A Retrospective Cohort Study.

OBJECTIVE: Postexercise vagal dysfunction is linked to noncardiovascular mortality in hemodialysis patients, but the mechanism is unknown. This study aimed to determine the association of cardiovagal neuropathy with systemic inflammation, protein-energy wasting, and noncardiovascular hospitalization. METHODS: This 2-center retrospective cohort study analyzed data from 280 hemodialysis patients who underwent exercise test. Patients were assessed for heart rate (HR) recovery (bpm) for 1 minute after exercise, a marker of vagal function, and were divided into 3 categories (Low: ≤ 6, Mid: 7-11, High: ≥ 12 bpm). We followed 1-year changes in the systemic inflammation-based prognostic score (Glasgow Prognostic Score [GPS]), body weight, and creatinine generation rate (CGR), an indicator of muscle mass, as well as 2-year hospitalization. RESULTS: The HR recovery category was associated with serum C-reactive protein and albumin levels and GPS. After 1 year, the low HR recovery category was associated with worsening in GPS (low, 0 [0-0.5]; mid, 0 [0-1]; high, 0 [0-0]), weight (low, 100.0 [96.1-102.5]; mid, 101.3 [98.9-105.0]; high, 100.5 [98.2-102.9]%), and CGR (low, 97.0 [88.5-111.4]; mid, 110.2 [90.9-124.8]; high, 106.2 [95.5-115.5]%), and the correlations with GPS and CGR remained consistent after adjusting for confounders such as exercise capacity and hospitalization during the follow-up period. There were 117 patients hospitalized. Compared to the high HR recovery category, the mid (hazard ratio: 1.8, 95% confidence interval [CI]: 1.1-3.1, P = .02) and low (hazard ratio: 2.4, 95% CI: 1.5-4.0, P = .001) categories were independently associated with an increased risk of all-cause hospitalization. For noncardiovascular disease hospitalization, the low HR recovery category was independently associated with increased risk of hospitalization (hazard ratio: 2.1, 95% CI: 1.2-3.7, P = .007). CONCLUSIONS: Vagal neuropathy in this population can contribute to adverse outcomes associated with systemic inflammation and protein-energy wasting.

Relationships between frailty and exercise capacity in patients undergoing hemodialysis: A cross-sectional study.

AIM: Hemodialysis (HD) patients have a high prevalence of frailty. The association between frailty and exercise capacity in HD patients has not been established. This study aimed to clarify the relationships between frailty and exercise capacity in HD patients. METHODS: This two-center cross-sectional study included HD patients who performed cardiopulmonary exercise testing. Participants were divided by frailty phenotype into robust, pre-frail, and frail using the revised Japanese version of the Cardiovascular Health Study criteria. Peak oxygen uptake (peakVO2 ) measured by cardiopulmonary exercise testing was compared with each frailty phenotype. The association between peakVO2 and frailty phenotype was analyzed using multivariate linear regression analysis adjusted for age, sex, body mass index diabetes mellitus, cardiovascular disease, cancer, history of fracture, hemoglobin, left ventricle ejection fraction, and percentage of heart rate reserve. RESULTS: The study included 136 patients (median age, 71.0 years; female, 23.5%), with 15.4%, 44.9%, and 39.7% with frailty phenotypes robust, pre-frail, and frail, respectively. PeakVO2 decreased with deterioration of the frailty phenotype (robust, median 15.1 [13.7-18.3] mL/min/kg; pre-frail, median 12.2 [10.5-14.4] mL/min/kg; frail, median 10.6 [9.2-12.5] mL/min/kg, P < 0.05). PeakVO2 decline was significantly associated with frail (B = -2.19, P = 0.004). Modeling individual frailty components showed a significant association between peakVO2 , usual gait speed (B = 2.38, P = 0.04), and low physical activity (B = -1.44, P = 0.004). CONCLUSION: Frailty in HD patients was associated with a decline in exercise capacity. HD patients with frailty need to improve exercise capacity, gait speed, and physical activity. Geriatr Gerontol Int 2023; 23: 795-802.

Beneficial effects of dantrolene in the treatment of rhabdomyolysis as a potential late complication associated with COVID-19: a case report.

BACKGROUND: Patients with severe COVID-19 have disorders of the respiratory, cardiovascular, coagulation, skeletal muscle, and central nervous systems. These systemic failures may be associated with cytokine release syndrome, characterized by hyperpyrexia, thrombocytopenia, hyperferritinemia, and the elevation of other inflammatory markers. Rhabdomyolysis with high fever is a complication that is rarely found in COVID-19. The exact relations of these clinical conditions in patients with COVID-19 remain unknown. CASE PRESENTATION: We present the case of a 36-year-old man with severe COVID-19 complicated by rhabdomyolysis and high fever. After admission, his condition continued to deteriorate, with a high body temperature. On day 9, the patient had elevated creatine kinase and myoglobin levels consistent with rhabdomyolysis (26,046 U/L and 3668 ng/mL, respectively). In addition to viral therapy, he was immediately treated with hydration. However, the patient had persistent fever and elevated creatine kinase levels. The patient was diagnosed with malignant hyperthermia as a late complication of COVID-19, although he had no hereditary predisposition to malignant hyperthermia or neuroleptic malignant syndrome. The administration of dantrolene with muscle relaxation and anti-inflammatory function showed potential efficacy for rhabdomyolysis, high fever, and increased plasma inflammatory markers. CONCLUSIONS: Malignant hyperthermia is triggered by not only anesthetic agents but also viral infections. A possible mechanism of malignant hyperthermia is hypersensitivity of calcium release from the sarcoplasmic reticulum. These include mutations in or the activation of the skeletal muscle ryanodine receptor calcium release channel. Dantrolene is a ryanodine receptor antagonist and is used as an anti-inflammatory agent. The administration of dantrolene showed potential efficacy for rhabdomyolysis, high body temperature due to inflammation, and increased inflammatory markers. The underlying mechanism of the association of rhabdomyolysis and high fever in COVID-19 might be similar to the pathogenesis of malignant hyperthermia.

Generation of Cellular Reactive Oxygen Species by Activation of the EP2 Receptor Contributes to Prostaglandin E2-Induced Cytotoxicity in Motor Neuron-Like NSC-34 Cells.

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease characterized by progressive degeneration of motor neurons in the central nervous system. Prostaglandin E2 (PGE2) plays a pivotal role in the degeneration of motor neurons in human and transgenic models of ALS. We have shown previously that PGE2 directly induces neuronal death through activation of the E-prostanoid (EP) 2 receptor in differentiated NSC-34 cells, a motor neuron-like cell line. In the present study, to clarify the mechanisms underlying PGE2-induced neurotoxicity, we focused on generation of intracellular reactive oxygen species (ROS) and examined the effects of N-acetylcysteine (NAC), a cell-permeable antioxidant, on PGE2-induced cell death in differentiated NSC-34 cells. Dichlorofluorescein (DCF) fluorescence analysis of PGE2-treated cells showed that intracellular ROS levels increased markedly with time, and that this effect was antagonized by a selective EP2 antagonist (PF-04418948) but not a selective EP3 antagonist (L-798,106). Although an EP2-selective agonist, butaprost, mimicked the effect of PGE2, an EP1/EP3 agonist, sulprostone, transiently but significantly decreased the level of intracellular ROS in these cells. MTT reduction assay and lactate dehydrogenase release assay revealed that PGE2- and butaprost-induced cell death were each suppressed by pretreatment with NAC in a concentration-dependent manner. Western blot analysis revealed that the active form of caspase-3 was markedly increased in the PGE2- and butaprost-treated cells. These increases in caspase-3 protein expression were suppressed by pretreatment with NAC. Moreover, dibutyryl-cAMP treatment of differentiated NSC-34 cells caused intracellular ROS generation and cell death. Our data reveal the existence of a PGE2-EP2 signaling-dependent intracellular ROS generation pathway, with subsequent activation of the caspase-3 cascade, in differentiated NSC-34 cells, suggesting that PGE2 is likely a key molecule linking inflammation to oxidative stress in motor neuron-like NSC-34 cells.

Severe Hypertriglyceridemia Possibly Masked Acute Pancreatitis and Led to a Difficult Diagnosis in an Obese Patient with Ketoacidosis-onset Type 2 Diabetes.

A young obese man with ketoacidosis-onset type 2 diabetes mellitus, associated with severe hypertriglyceridemia, was admitted to a local hospital complaining of abdominal pain. Although the abdominal pain worsened, his serum amylase level remained normal with persistent severe hypertriglyceridemia until the second day of hospitalization. The next day, computed tomography showed severe acute pancreatitis (AP) with serum amylase elevation, while the patient's triglyceride level decreased to 558 mg/dL. He was transferred to our hospital and recovered after intensive care. AP accompanied by diabetic ketoacidosis is not rare but an early diagnosis can be difficult to make due to normal amylase levels in the presence of severe hypertriglyceridemia.